Efficacy of a computer-aided detection system in a fecal immunochemical test-based organized colorectal cancer screening program: a randomized controlled trial (AIFIT study).

BACKGROUND: Computer-aided detection (CADe) increases adenoma detection in primary screening colonoscopy. The potential benefit of CADe in a fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening program is unknown. This study assessed whether use of CADe increases the adenoma detection rate (ADR) in a FIT-based CRC screening program. METHODS: In a multicenter, randomized trial, FIT-positive individuals aged 50-74 years undergoing colonoscopy, were randomized (1:1) to receive high definition white-light (HDWL) colonoscopy, with or without a real-time deep-learning CADe by endoscopists with baseline ADR > 25 %. The primary outcome was ADR. Secondary outcomes were mean number of adenomas per colonoscopy (APC) and advanced adenoma detection rate (advanced-ADR). Subgroup analysis according to baseline endoscopists' ADR (≤ 40 %, 41 %-45 %, ≥ 46 %) was also performed. RESULTS: 800 individuals (median age 61.0 years [interquartile range 55-67]; 409 men) were included: 405 underwent CADe-assisted colonoscopy and 395 underwent HDWL colonoscopy alone. ADR and APC were significantly higher in the CADe group than in the HDWL arm: ADR 53.6 % (95 %CI 48.6 %-58.5 %) vs. 45.3 % (95 %CI 40.3 %-50.45 %; RR 1.18; 95 %CI 1.03-1.36); APC 1.13 (SD 1.54) vs. 0.90 (SD 1.32; P  = 0.03). No significant difference in advanced-ADR was found (18.5 % [95 %CI 14.8 %-22.6 %] vs. 15.9 % [95 %CI 12.5 %-19.9 %], respectively). An increase in ADR was observed in all endoscopist groups regardless of baseline ADR. CONCLUSIONS: Incorporating CADe significantly increased ADR and APC in the framework of a FIT-based CRC screening program. The impact of CADe appeared to be consistent regardless of endoscopist baseline ADR.

Histologic heterogeneity and syndromic associations of non-ampullary duodenal polyps and superficial mucosal lesions.

BACKGROUND: Duodenal polyps and superficial mucosal lesions (DP/SMLs) are poorly characterised. AIMS: To describe a series of endoscopically-diagnosed extra-ampullary DPs/SMLs. METHODS: This is a retrospective study conducted in a tertiary referral Endoscopy Unit, including patients who had DPs or SMLs that were biopsied or removed in 2010-2019. Age, gender, history of familial polyposis syndromes, DP/SML characteristics were recorded. Histopathological, immunohistochemical and molecular analyses were performed. RESULTS: 399 non-ampullary DP/SMLs from 345 patients (60.6% males; median age 67 years) were identified. Gastric foveolar metaplasia represented the most frequent histotype (193 cases, 48.4%), followed by duodenal adenomas (DAs; 77 cases, 19.3%). Most DAs (median size 6 mm) were sessile (Paris Is; 48%), intestinal-type (96.1%) with low-grade dysplasia (93.5%). Among syndromic DAs (23%), 15 lesions occurred in familial adenomatous polyposis 1, two were in MUTYH-associated polyposis and one was in Peutz-Jeghers syndrome (foveolar-type, p53-positive, low-grade dysplasia). Only one (3.3%) tubular, low-grade DA showed mismatch repair deficiency (combined loss of MLH1 and PMS2, heterogeneous MSH6 expression), and it was associated with a MLH1 gene germline mutation (Lynch syndrome). CONCLUSION: DPs/SMLs are heterogeneous lesions, most of which showing foveolar metaplasia, followed by low-grade, intestinal-type, non-syndromic DAs. MMR-d testing may identify cases associated with Lynch syndrome.

Infection Control Practices and Outcomes of Endoscopy Units in the Lombardy Region of Italy: A Survey From the Italian Society of Digestive Endoscopy During COVID-19 Spread.

GOALS: The present survey from the Italian Society of Digestive Endoscopy (SIED-Società Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. BACKGROUND: Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. METHODS: A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. RESULTS: In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. CONCLUSIONS: Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

Pathologic substrate of gastropathy in Anderson-Fabry disease.

In both classic and late-onset AFD, mutations of the GLA gene cause deficient activity of the alpha-galactosidase enzyme resulting in intracellular accumulation of the undigested substrate. Gastrointestinal symptoms (GI) are common but non-specific and imputed to the AFD, irrespective of the demonstration of substrate accumulation in GI cells. We demonstrate substrate accumulation in gastric epithelial, vascular, and nerve cells of patients with classic AFD and, vice versa, absence of accumulation in late-onset AFD and controls.

Intestinal T-cell lymphoma with enteropathy-associated T-cell lymphoma-like features arising in the setting of adult autoimmune enteropathy.

Enteropathy-associated T-cell lymphoma is regarded as a dismal, late complication of coeliac disease, though a single case of T-cell lymphoma with such features arising in the setting of autoimmune enteropathy of the adult has been reported to date. We aim to describe the case of a 41-year-old woman complaining of severe malabsorption syndrome, who was diagnosed with autoimmune enteropathy based on the presence of flat intestinal mucosa unresponsive to any dietary restriction and positivity for enterocyte autoantibodies. Steroid therapy led to a complete recovery of both mucosal and clinical findings over 12 years, when disease relapse was accompanied by the appearance of monoclonal rearrangement of T-cell receptor-γ and peculiar T-cell phenotypic abnormalities, leading to a rapid transition to an overt T-cell lymphoma with features of the enteropathy-associated subtype. Despite intensive treatment, the patient developed cerebral metastasis and died 9 months later. Our case enhances the concept of enteropathy-associated T-cell lymphoma as a disease that may arise in the setting of enteropathies other than coeliac disease, thus representing a heterogeneous entity. Moreover, our observations support the need of a close follow-up of these patients, coupled with comprehensive characterization of mucosal biopsies.

Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin.

BACKGROUND & AIMS: Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin. METHODS: The transcriptional response of human duodenal mucosa to hepcidin was investigated using organ cultures of duodenal biopsies perendoscopically collected from healthy controls. Biopsies were cultured for 4 h with or without hepcidin-25 and were then assayed for the expression of iron-related genes. RESULTS: In samples that had not been exposed to hepcidin, correlations were found between the expression of genes involved in iron absorption: DMT1, Fpn1, Dcytb and HCP1. In ex vivo experiments hepcidin down-regulated mRNA levels of the iron transporters Fpn1, and DMT1, of the ferric reductase Dcytb, of the ferroxidase hephaestin, and of the putative heme carrier protein HCP1. CONCLUSIONS: Through the reported transcriptional changes hepcidin can modulate several steps of the iron absorption process, including the reduction of dietary iron by Dcytb, its uptake by enterocytes through DMT1, the mucosal uptake of heme iron by HCP1, and enterocyte iron release to plasma by Fpn1 in conjunction with hephaestin.

Innate and adaptive immunity in self-reported nonceliac gluten sensitivity versus celiac disease.

BACKGROUND: Immune mechanisms have been implicated in nonceliac gluten sensitivity (NCGS), a condition characterized by intestinal and/or extraintestinal symptoms caused by the ingestion of gluten in non-celiac/non-wheat allergic individuals. AIMS: We investigated innate and adaptive immunity in self-reported NCGS versus celiac disease (CD). METHODS: In the supernatants of ex vivo-cultured duodenal biopsies from 14 self-reported NCGS patients, 9 untreated and 10 treated CD patients, and 12 controls we detected innate cytokines - interleukin (IL)-15, tumor necrosis factor-α, IL-1ß, IL-6, IL-12p70, IL-23, IL-27, IL-32α, thymic stromal lymphopoietin (TSLP), IFN-α-, adaptive cytokines - interferon (IFN)-γ, IL-17A, IL-4, IL-5, IL-10, IL-13-, chemokines - IL-8, CCL1, CCL2, CCL3, CCL4, CCL5, CXCL1, CXCL10-, granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF). RESULTS: Mucosal innate and adaptive cytokines, chemokines and growth factors did not differ between self-reported NCGS, treated CD and controls. On the contrary, IL-6, IL-15, IL-27, IFN-α, IFN-γ, IL-17A, IL-23, G-CSF, GM-CSF, IL-8, CCL1 and CCL4 were significantly higher in untreated CD than in self-reported NCGS, treated CD and controls, while TSLP was significantly lower in untreated CD than in self-reported NCGS, treated CD and controls. CONCLUSION: In our hands, patients with self-reported NCGS showed no abnormalities of the mucosal immune response.

Is a detailed grading of villous atrophy necessary for the diagnosis of enteropathy?

AIMS: The utility of the 7 level Marsh-Oberhuber classification of mucosal damage in patients with coeliac disease has recently been criticised. Analysis of duodenal biopsies with dissecting microscopy is an unsophisticated method that, however, provides useful information in cases of frank villous atrophy. In the last 15 years, we have always analysed duodenal biopsies with dissecting microscopy before sending them to the pathology department for histology. If the results of dissecting microscopy and traditional histology were comparable, we feel that would be strong evidence that grading of the histological lesion would be unnecessary if not pointless in the everyday diagnosis of enteropathies. METHODS: The clinical notes of all 2075 patients undergoing duodenal biopsy between September 1999 and June 2015 were retrospectively analysed. Results of duodenal mucosal evaluation with both dissecting microscopy and traditional histology were collected and statistically compared. RESULTS: The κ statistics showed a substantial agreement of the two methods (κ statistics 0.78). Sensitivity of dissecting microscopy for detection of severe villous atrophy was 85.1% (95% CI 81.2% to 88.5%) and specificity was 95% (95% CI 93.8% to 96%). CONCLUSIONS: Although dissecting microscopy is an unsophisticated method that obviously cannot substitute traditional histology, our results suggest that in everyday clinical practice, the diagnosis of coeliac disease and other flat enteropathies does not require grading of villous atrophy.

A Wolf in Sheep's Clothing: A Sporadic Juvenile Polyp of the Colon Harboring an Intramucosal Adenocarcinoma.

We describe a solitary peduncolated polypoid lesion with a bilobated head in the transverse colon mucosa of a 51-year-old Caucasian man. Histologically, the lesion was consistent with juvenile polyp (JP), but showing a few dysplastic glands and a focus of intramucosal adenocarcinoma. This finding suggests that, at least in adults, even the sporadic JPs might carry an inherent potential for malignancy, which has so far only been pointed out for syndromic lesions. Additionally, we observed p53 overexpression in both the dysplastic lesions and in the invasive cells but not in the remaining epithelium. We can argue that p53 immunohistochemistry may be helpful in differentiating hyperplastic regenerative atypia of the epithelium, frequently found in JPs, from true dysplasia, a much more rare change in the sporadic JPs.

Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn's disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact.

INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained by a harmful T-cell response toward antigens of the gut microbiota in genetically susceptible subjects. Growing evidence highlights the safety and possible efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this condition. Therefore, we aimed to investigate the effects of bone marrow-derived MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell lines from both inflamed and non-inflamed colonic mucosal specimens of CD patients and from healthy mucosa of control subjects were grown with the antigen muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects were evaluated in terms of T-cell viability, apoptotic rate, proliferative response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3-dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL-tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA) targeting IDO. The relevance of cell-cell contact was evaluated by applying transwell membranes. RESULTS: A significant reduction in both cell viability and proliferative response to muramyl-dipeptide, with simultaneous increase in the apoptotic rate, was found in T cells from both inflamed and non-inflamed CD mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were co-cultured with MSCs. In parallel, an inhibitory effect was evident on the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interferon-γ, interleukin-17A and -21, whereas that of the transforming growth factor-ß and interleukin-6 were increased, and production of the tolerogenic molecule soluble HLA-G was high. These latter effects were almost completely eliminated by blocking the IDO, whose activity was upregulated in MSCs co-cultured with CD T cells. The use of a semipermeable membrane partially inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs were observed when T cells obtained from control subjects were used. CONCLUSION: MSCs exert potent immunomodulant effects on antigen-specific T cells in CD through a complex paracrine and cell-cell contact-mediated action, which may be exploited for widespread therapeutic use.

Increase in neuroendocrine cells in the duodenal mucosa of patients with refractory celiac disease.

OBJECTIVES: Several immune-mediated gastrointestinal disorders, including celiac disease (CD), are associated with neuroendocrine cell hyperplasia. However, neuroendocrine cells have never been explored in refractory CD (RCD). METHODS: Serial duodenal sections from 17 patients with RCD (6 type 1 and 11 type 2), 16 uncomplicated CD patients before and after gluten-free diet, 14 patients with potential CD, 27 patients with non-CD villous atrophy, i.e., common variable immunodeficiency (n=12), Whipple's disease (n=10) and giardiasis (n=5), and 16 healthy subjects were processed for the immunohistochemical detection of chromogranin A (CgA), serotonin, and somatostatin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative reverse transcription-PCR. Serum CgA and 24-h urine 5-hydroxyindoleacetic acid (5-HIAA) were assessed. Biopsies from treated CD patients were cultured with serotonin or peptic tryptic digest of gliadin (PT-gliadin), and interferon (IFN)-γ was detected by ELISA in culture supernatants. RESULTS: Epithelial cells positive for CgA and serotonin, but not somatostatin, were significantly increased in RCD. Raised mucosal transcripts of TpH-1, but not SERT, were found in RCD. On biopsies from treated CD patients, serotonin upregulated IFN-γ production at levels comparable to those induced by PT-gliadin. Serum CgA, but not urine 5-HIAA, was increased in RCD. No significant difference was found between RCD type 1 and type 2 in terms of neuroendocrine cells, mucosal TpH-1 transcripts, and serum CgA. CONCLUSIONS: Serotonin-producing neuroendocrine cells are increased in RCD mucosa. IFN-γ upregulation induced by serotonin suggests that this monoamine may have a role in sustaining the local inflammatory response in CD.

Endoscopic evaluation of gastrointestinal tract in patients with hereditary hemorrhagic telangiectasia and correlation with their genotypes.

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular dysplasia characterized by telangiectases and arteriovenous malformations. Three causative genes are known: ENG (HHT-1), ACVRL1 (HHT-2), and SMAD4 (mutated in HHT in association with juvenile polyposis). Gastrointestinal bleeding is the most common symptom after epistaxis. The stomach and the duodenum are the main gastrointestinal sites of telangiectases. Our aim was to explore gastrointestinal tract of consecutive HHT patients to assess distribution, number, size, and type of telangiectases in relation to genotype. METHODS: HHT patients underwent gastroduodenoscopy, video capsule endoscopy, and colonoscopy. Molecular analysis of ENG and ACVRL1 was performed to identify the disease-causing mutation. RESULTS: Twenty-two patients (13 men; mean age: 59 ± 9 years) were analyzed: 7 with HHT-1, 13 with HHT-2, and 2 undefined. Gastrointestinal telangiectases were identified as follows: at gastroduodenoscopy in 86% of HHT-1 patients and in 77% of HHT-2 patients, at video capsule endoscopy in all HHT-1 patients and in 84% of HHT-2 patients, and at colonoscopy in 1 patient for each group. HHT-1 showed multiple telangiectases with a higher prevalence, more relevant in the duodenum. CONCLUSION: Our data demonstrate extensive involvement of the gastrointestinal tract with a more severe association in HHT-1. Gastroduodenoscopy provides significant information on gastrointestinal involvement, and video capsule endoscopy may be added in selected patients. Colonic polyps/adenomas were identified as occasional findings.

Histologic changes in type A chronic atrophic gastritis indicating increased risk of neuroendocrine tumor development: the predictive role of dysplastic and severely hyperplastic enterochromaffin-like cell lesions.

The role of putative preneoplastic enterochromaffin-like cell lesions, either hyperplastic or dysplastic, in the genesis of type 1 enterochromaffin-like cell neuroendocrine tumors associated with type A chronic atrophic gastritis, their actual neoplastic risk, and their precise histogenetic mechanism deserve further clarification by specific histopathologic studies coupled with patient follow-up. A total of 100 patients with severe type A chronic atrophic gastritis, enterochromaffin-like cell hyperplasia, and antral G-cell hyperplasia were endoscopically and histologically followed up for a median of 90.1 months (total of 9118 person-months). Preneoplastic enterochromaffin-like cell lesions and newly developed neuroendocrine tumors were investigated histologically and histochemically, in parallel with enterochromaffin-like cell lesions found in nontumor mucosa of another 32 well-characterized and previously reported type 1 neuroendocrine tumors. Both neuroendocrine and nonneuroendocrine mucosa changes were analyzed and statistically evaluated. During follow-up, 7 of 100 patients developed neuroendocrine tumors: 5 were in a group of 20 cases with previous enterochromaffin-like cell dysplasia and 2 were among 80 cases showing only enterochromaffin-like cell hyperplasia throughout the study (hazard ratio, 20.7; P < .001). The severity of enterochromaffin-like cell hyperplasia at first biopsy, with special reference to linear hyperplasia with 6 chains or more per linear millimeter, also increased the risk of neuroendocrine tumor development during follow-up (hazard ratio, 13.0; P < .001). Enterochromaffin-like cell microinvasive dysplastic lesions arising at the epithelial renewal zone level, in connection with immature proliferating mucous-neck cells, were found to be linked to early intramucosal neuroendocrine tumor histogenesis. Both enterochromaffin-like cell dysplasia and severe hyperplasia indicate increased risk of neuroendocrine tumor development in type A chronic atrophic gastritis with hypergastrinemia/G-cell hyperplasia.

Mesenchymal stromal cell infusions as rescue therapy for corticosteroid-refractory adult autoimmune enteropathy.

Adult autoimmune enteropathy (AIE) is a rare cause of malabsorption syndrome unresponsive to dietary restriction. Its diagnostic hallmarks are small-bowel villous atrophy and antienterocyte autoantibodies. Therapy is based mainly on nutritional support and immunosuppression. We treated a 61-year-old woman with corticosteroid-refractory AIE and life-threatening malabsorption syndrome with systemic infusions of autologous, bone marrow-derived, mesenchymal stromal cells (MSCs) as rescue therapy. The MSCs were expanded ex vivo following a previously used Good Manufacturing Practice procedure, and 2 intravenous infusions of 1.8 × 10(6) MSCs/kg body weight were administered 2 weeks apart. Analysis of circulating and mucosal regulatory T-and B-cell numbers, and of serum and secretory immunoglobulin levels, was performed before and after treatment. The MSC infusions were safe and effective, leading to disappearance of disease hallmarks and recovery from the life-threatening condition. Increases in mucosal regulatory T-cell numbers and secretory immunoglobulin levels were also observed. The benefit, however, was transient, and a further MSC infusion resulted in the same short efficacy. This case encourages the use of MSCs to treat patients with life-threatening, corticosteroid-refractory AIE and suggests that MSC infusion can attenuate, albeit transiently, the autoimmune attack.

Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease.

OBJECTIVE: External fistulas represent a disabling manifestation of Crohn's disease with a difficult curability and a high relapse rate despite a large therapeutic armamentarium. Stem cell therapy is a novel and promising approach for treatment of chronic inflammatory conditions. We therefore investigated the feasibility, safety and efficacy of serial intrafistular injections of autologous bone marrow-derived mesenchymal stromal cells (MSCs) in the treatment of fistulising Crohn's disease. PATIENTS AND METHODS: We enrolled 12 consecutive outpatients (eight males, median age 32 years) refractory to or unsuitable for current available therapies. MSCs were isolated from bone marrow and expanded ex vivo to be used for both therapeutic and experimental purposes. Ten patients (two refused) received intrafistular MSC injections (median 4) scheduled every 4 weeks, and were monitored by surgical, MRI and endoscopic evaluation for 12 months afterwards. The feasibility of obtaining at least 50×106 MSCs from each patient, the appearance of adverse events, and the efficacy in terms of fistula healing and reduction of both Crohn's disease and perianal disease activity indexes were evaluated. In addition, the percentage of both mucosal and circulating regulatory T cells expressing FoxP3, and the ability of MSCs to influence mucosal T cell apoptosis were investigated. RESULTS: MSC expansion was successful in all cases; sustained complete closure (seven cases) or incomplete closure (three cases) of fistula tracks with a parallel reduction of Crohn's disease and perianal disease activity indexes (p < 0.01 for both), and rectal mucosal healing were induced by treatment without any adverse effects. The percentage of mucosal and circulating regulatory T cells significantly increased during the treatment and remained stable until the end of follow up (p < 0.0001 and p < 0.01, respectively). Furthermore, MSCs have been proven to affect mucosal T cell apoptotic rate. CONCLUSIONS: Locally injected MSCs represent a feasible, safe and beneficial therapy in refractory fistulising Crohn's disease.

Increased CD8+ intraepithelial lymphocyte infiltration and reduced surface area to volume ratio in the duodenum of patients with ulcerative colitis.

OBJECTIVE: Recent evidence suggests the involvement of the upper gastrointestinal tract in ulcerative colitis (UC). By conducting a prospective controlled study, we explored the immunological abnormalities in the duodenal mucosa of UC patients. METHODS: Duodenal and colonic biopsies were collected from 24 corticosteroid-free UC patients and 21 controls. Colonization by Helicobacter pylori and positivity for anti-endomysial antibodies was an exclusion criteria. The severity of duodenal and colonic inflammation was determined by endoscopic and histologic scores. Morphometry was performed to measure the surface area to volume ratio (SV). Duodenal CD3(+) and CD8(+) intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs) were detected by immunohistochemistry. RESULTS: Fifteen UC patients and 14 controls were Helicobacter pylori and anti-endomysial antibody negative and were thus included in the study. Microscopic duodenitis was reported in 4 of the 15 UC patients (26.6%), and in none of the controls. A significantly higher number of CD3(+) and CD8(+) IELs and LPMCs was found in UC patients than in controls. A significant positive correlation between the percentage of both CD3(+) and CD8(+) IELs and disease activity was found in UC patients. SV was significantly reduced in UC patients compared to controls, and inversely correlated with the percentage of CD8(+) IELs. CONCLUSIONS: The duodenum of UC patients is infiltrated by a higher number of CD8(+) IELs which correlates with the degree of villous flattening and disease activity, but not with extent of the colonic lesions. Further studies are needed to clarify whether the duodenum is a target organ in UC.

Type or extension of intestinal metaplasia and immature/atypical "indefinite-for-dysplasia" lesions as predictors of gastric neoplasia.

At present, no information exists on the neoplastic potential of the immature hyperproliferative and atypical lesions of the gastric mucosa, which have been recently labeled "indefinite for dysplasia." In addition, uncertainties still exist concerning the risk contribution of intestinal metaplasia (IM) type and extension, as well as Helicobacter pylori infection. In this study, 471 dyspeptic patients showing IM 10% or higher (median, 40; 25th-75th percentile, 20-60) in antral, angulus, or corpus endoscopic biopsies were submitted to repeated examinations (median, 3; 2-5) over 52 (26-85) months of follow-up, during which 44 neoplastic cases were recorded. IM extension, incomplete, sulfomucin-positive, or CAR5 antigen-positive IM; H pylori infection; and indefinite-for-dysplasia lesions (IDLs), as found at first examination, all showed significant neoplastic potential. However, only IDL, ongoing H pylori infection, and patient's age retained independent predictive power in a multivariate model. On the other hand, IM extension 20% or higher proved to be more sensitive as first screening parameter for identification of subjects with increased neoplastic risk. We suggest that patients with IM, when infected, should undergo H pylori eradication to reduce their cancer risk; only those bearing IDL or very extensive IM (which strongly correlates with IDL) should be followed up with endoscopies and biopsies.

Unusual association of neurofibromatosis type 1 and coeliac disease in a single patient.

Twenty-five per cent of patients with neurofibromatosis type 1 (NF1) have gastrointestinal involvement and malabsorption symptoms have been reported. We describe, for the first time, a patient with NF1, in whom gastrointestinal symptoms were due to coeliac disease (CD). Although this could be a coincidental association, we suggest that CD should be taken into account in the differential diagnosis of diarrhoea occurring in NF1 patients.

Gender and disease activity influence health-related quality of life in inflammatory bowel diseases.

BACKGROUND/AIMS: Measurement of health related quality of life (HRQoL) is a new tool to evaluate patients with inflammatory bowel disease (IBD). The aims of this study were to verify reliability and responsiveness of a disease-specific questionnaire [Italian Questionnaire on Quality of Life (IQQoL)], and to assess the relationship between clinical and demographic variables and HRQoL in IBD patients. METHODOLOGY: The IQQoL was submitted to all IBD patients consecutively seen at eight participating Hospitals, and re-administered at follow-up visits. The IQQoL covers intestinal and systemic symptoms, emotional and social function. The higher the score, the worse the HRQoL. RESULTS: 249 patients were enrolled, 106 with Crohn's disease (CD) and 143 with ulcerative colitis (UC). IQQoL was re-administered to 134 patients: 98 with unchanged, 17 with worsened and 19 with improved disease activity. The IQQoL was stable over time in patients with stable clinical conditions, and very responsive to change both in patients with improved and worsened disease activity. HRQoL was inversely correlated with disease activity, both in CD and UC. Perception of HRQoL was significantly worse in women than in men. CONCLUSIONS: The IQQoL is a reliable and responsive instrument to assess HRQoL in IBD patients. Active disease is related to poor HRQoL perception. In CD, women, mainly if young, have a worse HRQoL perception than men.